Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems

ABSTRACT

Methods, devices, systems, and kits are provided that buffer the time spaced glucose signals in a memory, and when a request for real time glucose level information is detected, transmit the buffered glucose signals and real time monitored glucose level information to a remotely located device, process a subset of the received glucose signals to identify a predetermined number of consecutive glucose data points indicating an adverse condition such as an impending hypoglycemic condition, confirm the adverse condition based on comparison of the predetermined number of consecutive glucose data points to a stored glucose data profile associated with the adverse condition, where confirming the adverse condition includes generating a notification signal when the impending hypoglycemic condition is confirmed, and activate a radio frequency (RF) communication module to wirelessly transmit the generated notification signal to the remotely located device only when the notification signal is generated.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/520,255, filed Oct. 21, 2014, which is acontinuation-in-part of U.S. patent application Ser. No. 14/028,372,filed Sep. 16, 2013, which claims the benefit of U.S. Provisional PatentApplication No. 61/702,227, filed Sep. 17, 2012. The present applicationalso claims the benefit of U.S. Provisional Application No. 61/896,314,filed Oct. 28, 2013. The disclosures of all of which are incorporatedherein by reference in their entireties for all purposes.

BACKGROUND

The detection of the concentration level of glucose or other analytes incertain individuals is vitally important to their health. For example,the monitoring of glucose levels is particularly important toindividuals with diabetes or pre-diabetes. People with diabetes may needto monitor their glucose levels to properly control their glycemiclevels.

Devices such as sensors have been developed for continuous and automaticin vivo monitoring of analyte characteristics, such as glucose levels,in bodily fluids such as in the blood stream or in interstitial fluid.Some of these analyte measuring sensors are configured so that at leasta portion of the devices are positioned below a skin surface of a user,e.g., in a blood vessel or in the subcutaneous tissue of a user.Information obtained from such devices can provide real time analytelevels which can indicate detected levels that require immediateattention, including intervention. It would be desirable to have an invivo analyte monitoring system which provides warnings or notificationsof onset of adverse physiological conditions detected by the analytemonitoring system such as hypoglycemic conditions.

SUMMARY

Provided herein are methods, apparatuses, systems and kits for in vivomonitoring of analyte levels that include, for example, wearable on bodysensor electronics operatively coupled to a transcutaneously positionedin vivo analyte sensor for real time in vivo monitoring of analytelevels, where the sensor electronics includes programming to detect andgenerate adverse condition notification such as detection ofhypoglycemic condition, hyperglycemic conditions, rapidly changingglucose levels, or other adverse medical conditions in the case of aglucose monitoring system, based on which, the sensor electronicsactivates its radio frequency (RF) communication module to transmit thegenerated notification to a user interface device such as a readerdevice or other electronic data communication/processing devices that isremote to the sensor electronics, to notify the user of the detectedadverse condition. In all other instances, sensor electronicscommunication lays dormant and only transmits sensed information when itreceives a signal from its external receiving device, as determined by auser. In this manner, critical sensing information is identified andcommunicated immediately, while all other sensing information is onlycommunicated when a user wants it.

In some embodiments, methods are implemented using one or more computerprocessors. The methods include receiving time spaced glucose signalsfrom an in vivo positioned glucose sensor in fluid contact withinterstitial fluid (or other bodily fluid), buffering the received timespaced glucose signals in a memory, detecting a request for real timeglucose level information, where when the request for real time glucoselevel information is detected, transmitting the buffered glucose signalsand/or real time glucose signal received from the glucose sensor to aremotely located device using a first or non hypoglycemic communicationprotocol such as backscattering radio wave, processing a subset of thereceived time spaced glucose signals to identify a predetermined numberof consecutive glucose data points from the subset of the received timespaced glucose signals indicating a hypoglycemic condition or animpending hypoglycemic condition, confirming the hypoglycemic conditionor impending hypoglycemic condition based on comparison of thepredetermined number of consecutive glucose data points to a storedglucose data profile associated with the impending hypoglycemiccondition, where confirming the impending hypoglycemic conditionincludes generating a notification signal when the impendinghypoglycemic condition is confirmed, and activating a secondcommunication protocol or hypoglycemic communication protocol such as aradio frequency (RF) communication module to wirelessly transmit thegenerated notification signal to the remotely located device only whenthe notification signal is generated.

In some other embodiments, apparatus includes a user interface, one ormore processors coupled to the user interface and a memory storingprocessing instructions. The instructions, when executed by the one ormore processors, cause the one or more processors to execute theaforementioned method.

In yet other embodiments, an integrated analyte monitoring assemblyincludes an analyte sensor designed for whole or partial positioning(i.e., transcutaneous positioning) through a skin layer and for beingmaintained in in vivo fluid contact with an interstitial fluid (orother) under the skin layer during a predetermined time period, theanalyte sensor having a proximal portion and a distal portion, andsensor electronics coupled to the analyte sensor. The sensor electronicsinclude a circuit board having a conductive layer and a sensor antennadisposed on the conductive layer, one or more electrical contactsprovided on the circuit board and coupled with the proximal portion ofthe analyte sensor to maintain continuous electrical communication, anda data processing component provided on the circuit board and in signalcommunication with the analyte sensor. The data processing component isconfigured to execute one or more routines for processing signalsreceived from the analyte sensor. The data processing component isconfigured to detect a radio frequency (RF) power signal, and transmitbuffered glucose data and/or real time glucose information generatedfrom an in vivo glucose sensor to a remotely located device, using forexample, but not limited to a backscattering radio wave, only when theRF power signal is detected, to perform, using one or more processors,hypoglycemic or impending hypoglycemic condition detection includingcomparison of a subset of the buffered glucose data to a stored glucosedata profile, and confirmation of the hypoglycemic condition based onthe comparison, where when the hypoglycemic condition is confirmed, togenerate a notification signal and activating a radio frequency (RF)communication module to wirelessly transmit the generated notificationsignal to the remotely located device, where the RF communication moduleis only activated when the notification signal is generated, and toupdate glucose sensor life expiration data each time the notificationsignal is generated and transmitted such that the sensor life expirationis reduced with each generated notification signal by a predeterminedtime period.

Numerous other aspects and embodiments are provided. These otherfeatures and aspects of the embodiments of the present disclosure willbecome more fully apparent from the following detailed description, theappended claims, and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a block diagram of the in vivo analyte monitoring systemin accordance with some embodiments of the present disclosure;

FIG. 2 is a flowchart illustrating adverse condition notificationroutine executed in the on body unit sensor electronics in accordancewith one embodiment of the present disclosure;

FIG. 3 is a flowchart illustrating adverse condition notificationroutine executed in the on body unit sensor electronics in accordancewith another embodiment of the present disclosure;

FIG. 4 is a flowchart illustrating routine executed in the on body unitsensor electronics to process concurrent occurrence of adverse conditiondetection and real time glucose level information request in accordancewith some embodiments of the present disclosure;

FIG. 5 is a flowchart illustrating sensor expiration update routinebased on adverse condition detection executed in the on body unit sensorelectronics in accordance with some embodiments of the presentdisclosure;

FIG. 6 is a flowchart illustrating adverse condition notificationroutine executed in the sensor electronics in accordance with anotherembodiment of the present disclosure; and

FIG. 7 illustrates a routine for processing advertising packets fromsensor electronics to notify the detected anticipated adverse conditionwith increased transmission range in certain embodiments.

DETAILED DESCRIPTION

Embodiments of the present disclosure provide methods, apparatuses,assemblies, systems and kits for in vivo monitoring of analyte levelsthat include on body sensor electronics operatively coupled to ananalyte sensor for real time monitoring of analyte levels, where thesensor electronics includes, for example, application specificintegrated circuit (ASIC) with programming logic to analyze and processsignals from the analyte sensor for detection and generation of adversecondition notification such as detection of an adverse medical conditionsuch as a hypoglycemic condition or impending hypoglycemic condition,based on which, the ASIC is programmed to activate the radio frequency(RF) communication module provided in the sensor electronics of thesensor electronics to transmit the generated notification to a readerdevice to inform the user of the detected adverse condition. The analytesensor may include a transcutaneously positioned in vivo analyte sensor,a transdermal analyte sensor, a fully implantable analyte sensor, anamperometric sensor, a coulometric sensor, an electrochemical sensor, anoptical sensor, or the like, which can monitor analyte levels in realtime and provide an indication of such monitored analyte level by, forexample, generating a corresponding real time signal indicating themonitored analyte level.

Embodiments of the subject disclosure are described primarily withrespect to glucose monitoring devices and systems, but the describedembodiments may be applied to other analytes and analytecharacteristics. For example, other analytes that may be monitoredinclude, but are not limited to, acetyl choline, amylase, bilirubin,cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB),creatine, DNA, fructosamine, glutamine, growth hormones, hormones,ketones, lactate, oxygen, peroxide, prostate-specific antigen,prothrombin, RNA, thyroid stimulating hormone, and troponin. Theconcentration of drugs, such as, for example, antibiotics (e.g.,gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs ofabuse, theophylline, and warfarin, may also be monitored. In thoseembodiments that monitor more than one analyte, the analytes may bemonitored at the same or different times.

FIG. 1 depicts a block diagram of an in vivo analyte monitoring systemin accordance with some embodiments of the present disclosure. Referringto FIG. 1, in one embodiment, the analyte monitoring system 100 includessensor electronics 110 in signal communication with a reader device 120.Sensor electronics 110 is configured for temporary fixed placement on askin surface of the user, and operatively coupled to a transcutaneouslypositioned analyte sensor such as an in vivo glucose sensor. Additionaldetails of the analyte monitoring system such as the system 100described above can be found in U.S. patent application Ser. Nos.12/807,278 and 12/698,124, the disclosures of each of which areincorporated herein by reference for all purposes.

Referring to FIG. 1, sensor electronics 110 in certain embodimentsincludes hardware such as an ASIC including programming logic to analyzeand process the signals (e.g., current signals, voltage signals, or thelike) received from the analyte sensor, a memory to store or buffer theanalyzed and processed signals in addition to storing parameters fordata analysis (e.g., predetermined or programmed hypoglycemic level, andglucose directional variation (e.g., trend) determination algorithm),and a first data communication module such as a radio frequencyidentification (RFID) module for providing real time glucose data inresponse to an interrogation signal received from the reader device 120.Sensor electronics 110 in certain embodiments includes a separateadverse event communication module such as a radio frequency (RF)communication module in signal communication with the ASIC for thetransmission of the adverse condition detection such that, only when theASIC determines that a programmed adverse condition is present based onthe monitored real time analyte level information received from the invivo sensor, the adverse event communication module is activated ortransitioned from a sleep (low power inactive) state, to activate statefor autonomous (relative to the first data communication module)communication of the adverse condition notification or alert to thereader device 120. In certain embodiments, the reader device 120includes a mobile telephone that supports multiple operation modesincluding for example, (1) cell phone mode, (2) RF communication mode,and (3) RFID communication mode, for operation as a standalone mobiletelephone (supporting cell phone mode), and/or for operation as acommunication device (supporting RF and RFID communication modes) in theanalyte monitoring system 100 (FIG. 1) for communication with the sensorelectronics 110.

As described in further detail in conjunction with FIGS. 2-5, in certainembodiments, the ASIC of the sensor electronics provided in the sensorelectronics 110 of the analyte monitoring system 100 is configured toprocess and analyze signals received from the in vivo glucose sensor inreal time to determine whether any programmed adverse condition such ashypoglycemic or impending hypoglycemic condition is present based on theanalyzed sensor signals, and thereafter, upon determination of thepresence of such condition, generates a notification that is thentransmitted to the reader device 120. In this manner, the programmedlogic in the ASIC of the sensor electronics in the sensor electronics110 in certain embodiments autonomously monitors for programmed adverseconditions, and communicates the detected adverse condition to thereader device 120 so that the user or patient can make a timelycorrective action. That is, by autonomously monitoring for theprogrammed adverse condition, the sensor electronics in the sensorelectronics 110 performs sensor data processing to analyze the receivedsensor data and determine whether such adverse condition is present ornot, rather than merely communicating the sensor data to another devicelocated remote to the sensor electronics 110 (for example, the readerdevice) for sensor data analysis.

In certain embodiments, any version of Bluetooth® can be used forcommunication between sensor electronics 110 and reader device 120. Forexample, in certain embodiments data communication between sensorelectronics 110 and reader device 120 includes Bluetooth® Low Energy(BTLE, BLE), also referred to as Bluetooth® SMART or Bluetooth® SMARTReady. A version of BTLE is described in the Bluetooth® Specification,version 4.0, published Jun. 30, 2010, which is incorporated by referenceherein for all purposes.

In certain embodiments, the ASIC of the sensor electronics 110 sensorelectronics includes programming logic to update the sensor expirationinformation with each detection of adverse condition and transmission ofcorresponding notification. For example, in certain embodiments, theexpiration of a sensor may be programmed into the sensor electronicsand/or reader unit to notify a user and/or disable usage after theexpiration. In some embodiments, the sensor expiration time period isreduced with each detection of adverse condition and transmission ofcorresponding notification because each detection of adverse conditionand transmission of the adverse condition notification consumes power inthe sensor electronics (e.g., the battery provided in the sensorelectronics 110) which is also necessary to power the sensor during thein vivo use period of the sensor in certain embodiments. The ASIC mayinclude programming to reduce an expiration time period by a presetamount each time an adverse condition is detected, and the notificationis transmitted to the reader device 120. For example, a sensor may havea predetermined expiration period defined as a time starting from sensormanufacture or insertion or initialization of a day, multiple days, aweek, multiple weeks, a month, multiple months, a year, or longer. Forexample, a sensor may have a 14 day useful life starting from sensorinsertion or initialization, and the ASIC may include programming toreduce the 14 day in vivo sensor life by a preset amount (such as 1minute, 5 minutes, 10 minutes, 15 minutes or 30 minutes, for example)each time an adverse condition is detected and a notification istransmitted to the reader device 120.

The various processes described above, including the processes operatingin the software application execution environment in the analytemonitoring system, including the sensor electronics of the sensorelectronics and/or the reader device performing one or more routinesdescribed above may be embodied as computer programs developed using anobject oriented language that allows the modeling of complex systemswith modular objects to create abstractions that are representative ofreal world, physical objects and their interrelationships. The software(e.g., instructions) required to carry out the inventive process, whichmay be stored in a memory or storage device of the storage unit of thevarious components of the analyte monitoring system described above inconjunction with the drawing, including the sensor electronics or thereader device, may be developed by a person of ordinary skill in the artand may include one or more computer program products.

FIG. 2 is a flowchart illustrating adverse condition notificationroutine executed in the sensor electronics in accordance with oneembodiment of the present disclosure. Referring to FIGS. 1-2, timespaced signals from glucose sensor is received and stored by the sensorelectronics (210) under the control of the ASIC programming logic. Asubset of the stored time spaced sensor signals is retrieved (220), andthe retrieved sensor signals are analyzed in accordance with programmedor stored algorithm(s) by the ASIC in the sensor electronics of thesensor electronics 110 based on an adverse condition parameter that isstored in sensor electronics (230). For example, in certain embodiments,the ASIC of the sensor electronics is programmed to retrieve a signalreceived from the sensor indicative of the real time analyte level, anda predetermined number of stored glucose level information based onsignals received from the analyte sensor, to determine whether anadverse condition is present (240).

That is, in certain embodiments, the ASIC is programmed to retrieve apredetermined number of sensor signals including the most temporallycurrent sensor signals, each signal obtained at a fixed and/or variabletime interval, to determine if at least a subset number of thepredetermined number of temporally adjacent sensor signals are below orabove a set threshold level indicating a corresponding adversecondition. For example, a most recently generated sensor signal andprior four sensor signals, each signal obtained at one minute intervals,to span a five minute period of monitored glucose level, and todetermine if at least three of the five temporally adjacent glucoselevels are below the hypoglycemic threshold level (for example, below 60mg/dL, or some other suitable/desired level stored in the sensorelectronics). If the ASIC determines that the at least three of the fivetemporally adjacent glucose levels is below the hypoglycemic thresholdlevel (that is, the monitored glucose level is below 60 mg/dL for atleast three consecutive minutes), the ASIC of the sensor electronicsgenerates a notification data which can be a single data bitrepresentative of an adverse condition alert (250). Then, using an RFcommunication module of the sensor electronics that is activated by theprogramming logic in the ASIC, transmits the notification data to thereader device 120 (FIG. 1) over an RF communication link using the RFcommunication module (260). If the ASIC determines that the analyzeddata does not indicate hypoglycemia, then no transmission is activated.

Referring back to FIG. 2, if the adverse condition is not detected (240)based on the analysis of the retrieved subset of the stored time spacedsensor signals, then the subset of stored signals for retrieval isupdated (270), and the routine returns to retrieve the stored timespaced sensor signals based on the updated subset. That is, in certainembodiments, the updated subset of sensor signals for retrieval andanalysis by the ASIC programming logic may include time shiftedconsecutive sensor signals (for example, the new sensor signal obtainedfrom the sensor and the prior four stored sensor signals). In otherembodiments, the subset of sensor signals for retrieval may be increasedor decreased so that more or less sensor signals, respectively, areretrieved for adverse condition analysis.

FIG. 3 is a flowchart illustrating adverse condition notificationroutine executed in the sensor electronics in accordance with anotherembodiment of the present disclosure. Referring to FIG. 3, the ASICprogramming logic of the sensor electronics 110 (FIG. 1) in oneembodiment receives and stores time spaced signals from thetranscutaneously positioned analyte sensor such as glucose sensor (310)and, using one or more algorithms stored in the sensor electronics, theASIC logic calculates a rate of change of the glucose level based on asubset of received and stored time spaced sensor signals (320). Thedetermined rate of change of the glucose level is then analyzed by theASIC logic based on stored adverse condition parameter (330) toascertain the detection of an anticipated adverse condition such as animpending hypoglycemic condition based on the rate of change of theglucose level (340). When the anticipated adverse condition is detected,ASIC is programmed to generate a corresponding notification data (350),and to activate the RF communication module of the sensor electronics110 (FIG. 1) to transmit the generated notification data (360) to thereader device 120.

Referring back to FIG. 3, if the anticipated adverse condition is notdetected based on the analysis of the rate of change calculation by theASIC programming logic based on the adverse condition parameter, theroutine returns to retrieve the next subset of time spaced sensorsignals to determine a new rate of change of glucose level. In certainembodiments, the adverse condition parameter stored in the sensorelectronics 110 may be a threshold rate of −2 mg/dL/min within a presetlevel from the stored hypoglycemic level (e.g., 60 mg/dL) such that whenthe current glucose level is at the stored preset glucose level, and thedetermined rate of change of at −2 mg/dL/min, a projection of theglucose level based on the determined rate of change will result in theglucose level crossing stored hypoglycemic level within a fixed timeperiod. Alternatively, the adverse condition parameter stored in thesensor electronics 110 may be a threshold rate of +2 mg/dL/min within apreset level from the stored hypoglycemic level (e.g., 180 mg/dL) suchthat when the current glucose level is at the stored preset glucoselevel, and the determined rate of change of at +2 mg/dL/min, aprojection of the glucose level based on the determined rate of changewill result in the glucose level crossing stored hypoglycemic levelwithin a fixed time period. While specific numerical examples areprovided above, within the scope of the present disclosure, othersuitable rates of changes and threshold levels are contemplated such as,for example, +/−2.5 mg/dL/min, +/−3 mg/dL/min; +/−3.5 mg/dL/min, or +/−4mg/dL/min.

Accordingly, the sensor electronics 110, in certain embodiments, isprogrammed to generate a notification based on the adverse conditionanalysis and transmit the notification to the reader device 120 to alertthe user or the patient to take necessary corrective actions. Within thescope of the present disclosure, the sensor electronics of the 110monitors for other conditions or parameters associated with the sensorelectronics 110 such as, but not limited to the sensor status (failuremode detection), sensor signal/data corruption, sensor dislodgingdetection, each based on a pre-programmed algorithm provided to thesensor electronics to monitor for and detect operating conditions of thesensor electronics 110. Upon monitoring and detection of the one or moreof such conditions or parameters of the sensor electronics 110, thesensor electronics of the present disclosure autonomously provides orcommunicates the detected condition/parameter to the remotely locatedreader device 120 (FIG. 1) or other suitable data communication device.

In accordance with certain embodiments of the present disclosure, theadverse condition determination by the sensor electronics of the 110 inthe analyte monitoring system 100 (FIG. 1) and subsequent communicationof notification to the reader device 120 is independent of the analytedata communication based on RFID communication where the ASIC of thesensor electronics in the 110 includes RFID module to provide real timeanalyte level information to the reader device 120 in response to andwhen the interrogation signal is received from the reader device 120 asdetermined by the user of the device. In this manner, the ASIC in thesensor electronics of the 110 is configured to control the operation ofthe sensor electronics and process sensor signals such that real timeglucose data is provided upon request by the reader device 120, and inaddition, autonomously determine adverse conditions based on monitoredanalyte levels, and to transmit notification to reader device using aseparate RF communication module.

FIG. 4 is a flowchart illustrating routine executed in the sensorelectronics to process a concurrent occurrence of an adverse conditiondetection and a real time glucose level information request inaccordance with some embodiments of the present disclosure. Referring toFIG. 4, in certain embodiments, sensor electronics in the sensorelectronics 110 (FIG. 1) receives an interrogation signal or requestfrom the reader device 120 for current real time and/or buffered/storedanalyte level information (410). Concurrently, the sensor electronics110 generates adverse condition notification data for transmission basedon the analysis of the monitored analyte level (420). In certainembodiments, the ASIC programming logic of the sensor electronics 110 isprogrammed to prioritize between the transmission of the real timeanalyte level information (RFID communication) and the adverse conditionnotification (RF communication) by selecting the RFID response datapacket to provide to the reader device 120 and suppress the activationof the RF communication module in the sensor electronics 110 (ormaintain the RF communication module in inactive state (430)). In thiscase, the output of the current analyte level on the reader device 120based on the communication of the response to the interrogation signal(440) provides the real time analyte level such as glucose level, sothat the user will be notified of any adverse or potentially adversecondition based on the real time glucose level.

FIG. 5 is a flowchart illustrating sensor expiration update routinebased on adverse condition detection executed in the sensor electronicsin accordance with some embodiments of the present disclosure. Referringto FIG. 5, when adverse condition notification data is transmitted withthe RF communication module in the sensor electronics 110 (510), ASICprogramming logic in certain embodiments retrieves the analyte sensorexpiration information from memory or storage device of the sensorelectronics (520), and updates the retrieved analyte sensor expirationinformation by a preset, programmed time period so that the sensor lifeis effectively reduced upon occurrence of each adverse conditionnotification data transmission (530). After updating the sensorexpiration information, if it is determined that the sensor life has notexpired (540), the routine returns to detect whether adverse conditionnotification data is transmitted (510) as described, for example, inconjunction with FIGS. 2-4 above. On the other hand, if it is determinedthat the sensor life has expired based on the updated sensor expirationinformation (540), real time analyte sensor data processing in sensorelectronics 110 by the ASIC programming logic is disabled (550) (and/orthe user interface presents an expiration indicator), so that subsequentRFID data packets in response to interrogation signals received from thereader device 120 (FIG. 1) do not include (in other words omit) current,real time monitored analyte level. However, communication of stored dataincluding stored glucose data, temperature data and the like may stillbe communicated to the reader device 120.

FIG. 6 is a flowchart illustrating adverse condition notificationroutine executed in the sensor electronics in accordance with anotherembodiment of the present disclosure. Referring to FIG. 6, the ASICprogramming logic in the sensor electronics 110 (FIG. 1) in oneembodiment receives and stores time spaced signals from thetranscutaneously positioned analyte sensor such as glucose sensor (610)and, using one or more algorithms stored in the sensor electronics, theASIC logic determines a rate of change of the glucose level based on asubset of received and stored time spaced sensor signals (620). Thedetermined rate of change of the glucose level is then analyzed by theASIC logic based on stored adverse condition parameter (630) toascertain the detection of an anticipated adverse condition such as animpending hypoglycemic condition based on the rate of change of theglucose level (640). When the anticipated adverse condition is detected,ASIC is programmed to generate a corresponding notification data (650),and to activate the RF communication module and increase the radio powerlevel in the sensor electronics 110 (FIG. 1) to transmit the generatednotification data (660) to the reader device 120 with a greatertransmission range than the transmission range of data from the sensorelectronics 110 to the reader device 120 during normal operation.Referring back to FIG. 6, if the anticipated adverse condition is notdetected based on the analysis of the rate of change calculation by theASIC programming logic based on the adverse condition parameter, theroutine returns to retrieve the next subset of time spaced sensorsignals to determine a new rate of change of glucose level.

In this manner, in certain embodiments, when an anticipated adversecondition based on monitored analyte levels such as hypoglycemiccondition or impending hypoglycemic condition, or any other appropriateor desired adverse condition is detected, sensor electronics 110 isconfigured to increase the transmit power level of the RF communicationmodule to reliably send the generated notification data indicating thedetection of the anticipated adverse condition to the reader device 120with a greater communication range. The increased transmit power levelin certain embodiments includes the highest possible power levelsupported by the sensor electronics and its power supply (e.g.,battery).

In certain embodiments, the data communication between sensorelectronics 110 and reader device 120 uses direct advertising mode ofthe Bluetooth® Low Energy (BTLE) protocol. The direct (or directed)advertising mode is a link layer mode of BTLE, and is typically carriedout through an advertising event, which includes for example,communication of one or more direct advertising packets on one or moreadvertising channels of the link layer of the BTLE packet structure(e.g., protocol data unit (PDU) header, PDU payload, CRC). Eachadvertising packet can be sent on the advertising channel at a specifiedtime interval. If sent on all three advertising channels provided byBTLE, the time interval between the sending of each consecutive requeston a different channel is 3.75 milliseconds (ms), and these repeatedtransmissions can persist for a predetermined length of time, e.g., aslong as 1.28 seconds as described more fully, for example, in section4.4.2.4 of Part B of the incorporated Bluetooth® Specification, version4.0, incorporated herein by reference. In certain embodiments, thenotification data corresponding to the detected anticipated adversecondition based on monitored analyte level is sent as a one bit alertmessage in the advertising packet from the sensor electronics 110, whichis received by the reader device 120 that has been programmed orconfigured to anticipate the time window for transmitting the alertmessage in the advertising packet using direct advertising mode. Thereader device 120 in certain embodiments is programmed to extract ordetermine sensor electronics 110 transmission time windows based onprior data communication received from sensor electronics 110.Additional details for determining data transmission timing windows andrandomization of advertising packet transmission intervals can be foundin U.S. Patent Publication No. 2013/0235166 published on Sep. 12, 2013,the disclosure of which is incorporated by reference herein for allpurposes.

When sensor electronics 110 detects or determines the anticipatedadverse condition based on the monitored analyte level, and generates orassembles the direct advertising packet including the one bit alertmessage, and transmits to the reader device 120, the reader device 120,since it knows when to look for the direct advertising packets fromsensor electronics based on the determined anticipated transmission timewindows as described above, awaits for the transmission, and receivesthe advertising packet including the alert message. Reader device 120 incertain embodiments is configured to apply the pulse matched filter tothe received advertising packets from the sensor electronics 110 andprocessing the packets as on-off keyed pulses and ignoring the GaussianFrequency Shift Keying (GSFK) modulation, the reader device 120 detectsand processes the alert message in the advertising packets from sensorelectronics 110 and appropriately notifies the user or the healthcareprovider.

More specifically, in certain embodiments, the advertising packet sentby the sensor electronics 110 includes a predetermined string of bits,or bit code, the reader device 120 ignores the GFSK modulation used bythe Bluetooth® radio chip (modulated at 1 Mbps), and receives theadvertising packets as on-off keyed pulses. This results in processinggain that uses multiple pulses to send one data symbol such that asignal sent over a wide bandwidth improves the communication link budgetby compressing that bandwidth into a smaller bandwidth. Morespecifically, in certain embodiments, the reader device 120 isconfigured to acquire or receive the stream of advertising packets fromsensor electronics and then apply a pulse matched filter to the receivedsequence of advertising packets, handled as on-off keyed pulses andignoring the GFSK modulation, and which covers the full 1.28 seconds oftransmission. In the 1.28 seconds of transmission, there are 341 directadvertising packets sent. There are 96 bits sent in a direct advertisingpacket, and only one bit is sent if one advertising packet is consideredas one bit. The processing gain is then equal to 10 Log(341)+10 Log(96)which is 45 decibels (dB). This is because the one bit-alert message(corresponding to the detected anticipated adverse condition) isintegrated across all the bits sent in all the packets in the full 1.28second direct advertising mode transmission in the same noise bandwidth.Given that the RF power decreases by the square of the transmissiondistance, the communication range improvement from this processing gaincan be as high as a factor of six to seven (without factoring inpotential losses from timing uncertainty and other potentialimpairments).

Turning to the Figures, FIG. 7 illustrates a routine for processingadvertising packets from sensor electronics to notify the detectedanticipated adverse condition with increased transmission range incertain embodiments. Referring to FIG. 7, advertising packets fromsensor electronics 110 are received by the reader device 120 (710), andthe reader device 120 determines data transmit time window based on thereceived advertising packets (720). For example, sensor electronics 110in certain embodiments includes information on the advertising packetsthat is used as a seed to randomize the advertising packet transmissionover the 0 to 10 ms range so that the reader device 120 is programmed toanticipate the advertising packet transmit time intervals. Referringback to FIG. 7, reader device 120 in certain embodiments is configuredto apply matched filter to the sequence of advertising packets receivedfrom sensor electronics 110 (730) to search for an alert message in theadvertising packet from sensor electronics 110 that corresponds to thedetected anticipated adverse condition based on monitored analyte level.When the alert message in the advertising packet is detected (740),reader device 120 in certain embodiments is configured to generate acorresponding notification data (750), for output to the user or thehealthcare provider including, for example, an audible notification, avisual notification, a vibratory notification, or one or morecombinations thereof. Referring again to FIG. 7, if the reader devicedoes not detect the alert message in the received advertising packetusing the pulse matched filter, in certain embodiments, the readerdevice 120 awaits for the next data transmission time interval toreceive and process (including applying matched filter) the advertisingpackets from the sensor electronics 110.

In certain embodiments, sensor electronics 110 is programmed to supportscheduled transmission of stored glucose data to the remotely locatedreader device 120 in the analyte monitoring system 100 (FIG. 1), forexample, preceding or following a particular event as a meal event,exercise event, and the like. In certain embodiments, the reader device120 can program or instruct the sensor electronics 110 with the timingof the scheduled transmission of the stored glucose data. For example,the user, manipulating the operation of the reader device 120 canprogram the sensor electronics 110 to transmit all or a portion of thestored glucose data before and after each scheduled meal event, orexercise event.

Accordingly, when the programmed event such as the scheduled meal eventor exercise event approaches, the sensor electronics 110 retrieves thestored glucose data and transmits to the remotely located reader device.Further, when the scheduled event has been completed (based on, forexample, time elapsed from the programmed start of the scheduled event),the sensor electronics 110 retrieves all or a portion of the storedglucose data (or in some cases, the incremental stored glucose datasince the last transmission of the glucose data at the beginning of thescheduled event) and again, transmits the retrieved glucose data to thereader device. In this manner, in certain embodiments, a snapshot ofglucose profile/measurements can be provided to the user in the contextof particular scheduled events based on which, the sensor electronics110 is programmed for glucose data communication. Within the scope ofthe present disclosure, other scheduled events are contemplated such assleep event, travel event, and further, each event can be furthersegmented, for example, where the meal event can be segmented asbreakfast event, lunch event and dinner event, each of which can have aparticular amount of time (preceding and/or following) for glucose datatransmission from the sensor electronics 110.

Additionally, in certain embodiments, with each scheduled datacommunication from the sensor electronics 110 to the remotely locatedreader device 120, the sensor electronics 110 battery life may bemonitored and reduced accordingly since each data communication from thesensor electronics 110 will consume battery power such that the use lifeof the sensor electronics 110 may be reduced.

In the manner described above, the analyte monitoring system 100(FIG. 1) in certain embodiments includes ASIC programming logic in thecompact sensor electronics 110 worn on the body of the user thatmonitors for adverse conditions based on the glucose signals from the invivo glucose sensor, and autonomously generates notification which iscommunicated to the reader device 120 when the adverse condition isdetected. The generated notification data in certain embodiments is asingle data bit which is communicated over a RF communication link. Inaddition to the notification data, stored and current glucose data andother related information such as temperature data may be transmittedusing the RF communication link. However, in certain embodiments, in theevent that the glucose data or other related data such as temperaturedata, sensor expiration data and the like are corrupted duringencryption/decryption or RF communication so that on the reader device120 the information is not retrievable, the adverse conditionnotification is still provided on the reader device 120 for output. Instill further embodiments, the RFID component and the RF communicationmodule of the sensor electronics 110 may be configured to share the sameantenna that supports RFID communication as well as RF communicationwith the reader device 120. In other embodiments, two or more separateantennas may be provided in the sensor electronics 110 to support theRFID data transfer and the RF communication with the reader device 120.

A method in one embodiment includes receiving time spaced glucosesignals from an in vivo glucose sensor in fluid contact withinterstitial fluid, buffering the received time spaced glucose signalsin a memory, detecting a request for real time glucose levelinformation, wherein when the request for real time glucose levelinformation is detected, transmitting the buffered glucose signals andreal time glucose signal received from the glucose sensor to a remotelylocated device using, for example, but not limited to, a backscatteringradio wave, processing a subset of the received time spaced glucosesignals to identify a predetermined number of consecutive glucose datapoints from the subset of the received time spaced glucose signalsindicating an impending hypoglycemic condition, confirming the impendinghypoglycemic condition based on comparison of the predetermined numberof consecutive glucose data points to a stored glucose data profileassociated with the impending hypoglycemic condition, wherein confirmingthe impending hypoglycemic condition includes generating a notificationsignal when the impending hypoglycemic condition is confirmed,activating a radio frequency (RF) communication module to wirelesslytransmit the generated notification signal to the remotely locateddevice only when the notification signal is generated.

In certain embodiments, the method includes transmitting the generatednotification signal and the time spaced glucose data concurrently,wherein only the generated notification signal is transmitted with theactivated RF communication module.

In certain embodiments, when the request for real time glucose levelinformation is detected at the same time as the confirmation of theimpending hypoglycemic condition, the method includes prioritizing datatransmission such that the generated notification signal is transmittedto the remotely located device after the transmission of the bufferedglucose signals and real time glucose signal.

In certain embodiments, wherein when the request for real time glucoselevel information is detected at the same time as the confirmation ofthe impending hypoglycemic condition, the method includes suppressingtransmission of the generated notification signal such that only thebuffered glucose signals and real time glucose signal are transmitted.

In certain embodiments, the method includes updating the glucose sensorexpiration information based on the number of generated notificationsignals during the in vivo use period of the glucose sensor, whereupdating the glucose expiration information includes subtracting apredetermined amount of time period from the glucose sensor expirationinformation for each generated notification signal such that the glucosesensor expiration information is shortened with each generatednotification signal.

A method in accordance with another embodiment includes detecting aradio frequency (RF) power signal, and transmitting buffered glucosedata and real time glucose information generated from an in vivo glucosesensor to a remotely located device using a backscattering radio waveonly when the RF power signal is detected, performing, using one or moreprocessors, hypoglycemic condition detection including comparing asubset of the buffered glucose data to a stored glucose data profile,and confirming the hypoglycemic condition based on the comparison,wherein when the hypoglycemic condition is confirmed, generating anotification signal and activating a radio frequency (RF) communicationmodule to wirelessly transmit the generated notification signal to theremotely located device, wherein the RF communication module is onlyactivated when the notification signal is generated, and updatingglucose sensor life expiration data each time the notification signal isgenerated and transmitted such that the sensor life expiration isreduced with each generated notification signal by a predetermined timeperiod.

In certain embodiments, when the RF power signal detection coincideswith when the notification signal is generated, the method includesprioritizing data transmission such that the generated notificationsignal is transmitted to the remotely located device prior totransmitting the buffered glucose data and the real time glucoseinformation.

In certain embodiments, the buffered glucose data and/or real timeglucose information are transmitted to the remotely located device usingradio frequency identification (RFID) data communication protocol, andthe notification signal is transmitted to the remotely located deviceusing RF data communication protocol.

In certain embodiments, the glucose sensor life expiration is subtractedby the predetermined time period with each generated notificationsignal.

In certain embodiments, the method also includes disabling datacommunication to the remotely located device when the glucose sensorlife has expired.

An apparatus for providing adverse condition notification in an analytemonitoring system in accordance with another embodiment includes an invivo glucose sensor transcutaneously positioned in fluid contact withinterstitial fluid, sensor electronics operatively coupled to theglucose sensor, the sensor electronics including a memory, a radiofrequency (RF) communication module, and an application specificintegrated circuit (ASIC), the ASIC having programming logic to bufferthe received time spaced glucose signals in the memory, to detect arequest for real time glucose level information, wherein when therequest for real time glucose level information is detected,transmitting the buffered glucose signals and/or real time glucosesignal received from the glucose sensor to a remotely located deviceusing, for example, but not limited to, a backscattering radio wave, toprocess a subset of the received time spaced glucose signals to identifya predetermined number of consecutive glucose data points from thesubset of the received time spaced glucose signals indicating animpending hypoglycemic condition, to confirm the impending hypoglycemiccondition based on comparison of the predetermined number of consecutiveglucose data points to a stored glucose data profile associated with theimpending hypoglycemic condition, wherein confirming the impendinghypoglycemic condition includes generating a notification signal whenthe impending hypoglycemic condition is confirmed, and to activate theRF communication module to wirelessly transmit the generatednotification signal to the remotely located device only when thenotification signal is generated.

In certain embodiments, the ASIC transmits the generated notificationsignal and the time spaced glucose data concurrently, where only thegenerated notification signal is transmitted with the activated RFcommunication module.

In certain embodiments, when the request for real time glucose levelinformation is detected at the same time as the confirmation of theimpending hypoglycemic condition, the ASIC prioritizes data transmissionsuch that the generated notification signal is transmitted to theremotely located device after to the transmission of the bufferedglucose signals and real time glucose signal.

In certain embodiments, when the request for real time glucose levelinformation is detected at the same time as the confirmation of theimpending hypoglycemic condition, the ASIC is programmed to transmit thebuffered glucose signals and real time glucose signal and to suppressthe communication of the generated notification signal.

In certain embodiments, the ASIC is programmed to update the glucosesensor expiration information based on the number of generatednotification signals during the in vivo use period of the glucosesensor, where the ASIC is programmed to subtract a predetermined amountof time period from the glucose sensor expiration information for eachgenerated notification signal such that the glucose sensor expirationinformation is shortened with each generated notification signal.

A glucose monitoring apparatus in accordance with another embodimentincludes an in vivo glucose sensor having a portion transcutaneouslypositioned in fluid contact with interstitial fluid, sensor electronicsincluding an application specific integrated circuit (ASIC) havingprogramming logic to detect a radio frequency (RF) power signal, and totransmit buffered glucose data and real time glucose informationgenerated from the glucose sensor to a remotely located device using,for example, but not limited to, a backscattering radio wave only whenthe RF power signal is detected, to perform hypoglycemic conditiondetection including comparing a subset of the buffered glucose data to astored glucose data profile, and to confirm the hypoglycemic conditionbased on the comparison, wherein when the hypoglycemic condition isconfirmed, to generate a notification signal and activate a radiofrequency (RF) communication module to wirelessly transmit the generatednotification signal to the remotely located device, wherein the RFcommunication module is only activated when the notification signal isgenerated, wherein the programming logic of the ASIC further includesupdating glucose sensor life expiration data each time the notificationsignal is generated and transmitted such that the sensor life expirationis reduced with each generated notification signal by a predeterminedtime period.

In certain embodiments, when the RF power signal detection coincideswith when the notification signal is generated, the programming logic ofASIC prioritizes data transmission such that the transmission of thegenerated notification signal to the remotely located device issuppressed so that only the buffered glucose data and the real timeglucose information is communicated to the remotely located device.

In certain embodiments, the buffered glucose data and real time glucoseinformation are transmitted to the remotely located device using radiofrequency identification (RFID) data communication protocol, and whereinthe notification signal is transmitted to the remotely located deviceusing RF data communication protocol.

In certain embodiments, the glucose sensor life expiration is subtractedby the predetermined time period with each generated notificationsignal.

In certain embodiments, the programming logic of the ASIC disables datacommunication to the remotely located device when the glucose sensorlife has expired.

In accordance with still a further embodiment, there is provided amethod of providing physiological data communication, comprisingreceiving time spaced glucose related signals from an in vivo glucosesensor in fluid contact with interstitial fluid, storing the receivedtime spaced glucose related signals in a memory, detecting apredetermined time remaining to the occurrence of a scheduled programmedevent, retrieving at least a portion of the stored received time spacedglucose related signals from the memory, and transmitting the retrievedat least a portion of the stored received time spaced glucose relatedsignals to a remote location.

In certain embodiments, the scheduled programmed event includes one ormore of a scheduled meal event, a sleep event, an exercise event, or atravel event.

In certain embodiments, retrieving at least a portion of the storedreceived time spaced glucose related signals from the memory includesretrieving the entire stored received time spaced glucose relatedsignals from the memory, and further including transmitting the entireretrieved stored received time spaced glucose related signals from thememory to the remote location.

In still further embodiments, detecting the predetermined time remainingto the occurrence of the scheduled programmed event includes monitoringtime remaining from the occurrence of the scheduled programmed event.

In yet further embodiments, the method includes determining thefrequency of the detection of the predetermined time remaining to theoccurrence of a scheduled programmed event, and transmission of theretrieved at least a portion of the stored received time spaced glucoserelated signals to the remote location, and adjusting the glucose sensorexpiration information based on the determined frequency of detection.

Various other modifications and alterations in the structure and methodof operation of the embodiments of the present disclosure will beapparent to those skilled in the art without departing from the scopeand spirit of the present disclosure. Although the present disclosurehas been described in connection with certain embodiments, it should beunderstood that the present disclosure as claimed should not be undulylimited to such embodiments. It is intended that the following claimsdefine the scope of the present disclosure and that structures andmethods within the scope of these claims and their equivalents becovered thereby.

1-28. (canceled)
 29. A computer-implemented method of providingnotification of an adverse condition associated with a monitored analytelevel, the method comprising: transmitting data indicative of themonitored analyte level using a first communication protocol; detectingthe adverse condition based on the monitored analyte level; generatingone or more advertising packets comprising a notification messagecorresponding to the monitored analyte level and informationcorresponding to a data transmit time window; and transmitting, using asecond communication protocol, the one or more advertising packetsaccording to the data transmit time window for a predetermined durationof time.
 30. The method of claim 29, wherein the one or more advertisingpackets are transmitted, using the second communication protocol, indirect advertising mode.
 31. The method of claim 29, wherein thedetected adverse condition includes one or more of an impendinghypoglycemic condition, a hypoglycemic condition, or a hyperglycemiccondition.
 32. The method of claim 29, wherein the data transmit timewindow is randomized.
 33. The method of claim 32, wherein the datatransmit time window is randomized based on a seed included in the oneor more advertising packets.
 34. The method of claim 29, wherein thenotification message is sent as a one bit alert message in the one ormore advertising packets.
 35. The method of claim 29, wherein the one ormore advertising packets are transmitted, using the second communicationprotocol, using a plurality of advertising channels.
 36. The method ofclaim 29, wherein the monitored analyte level is a monitored glucoselevel.
 37. The method of claim 29, wherein the first communicationprotocol comprises a radio frequency identification (RFID) protocol. 38.The method of claim 29, wherein the second communication protocolcomprises a Bluetooth or Bluetooth Low Energy protocol.
 39. Acomputer-implemented method of providing notification of an adversecondition associated with a monitored analyte level, the methodcomprising: receiving time spaced analyte related signals from an invivo analyte sensor in fluid contact with bodily fluid; transmitting, bya wireless communication module, one or more of the received time spacedanalyte related signals to a remotely located device at a first powerlevel from a power source coupled to the wireless communication module;buffering the received time spaced analyte related signals in a memory;processing the received time spaced analyte related signals to identifythe adverse condition and to generate a notification signal when theadverse condition is identified; in response to identifying the adversecondition, generating a notification signal, increasing the first powerlevel to a second power level from the power source, and wirelesslytransmitting, by the wireless communication module, the generatednotification signal to the remotely located device at the second powerlevel.
 40. The method of claim 39, wherein the second power level is amaximum radio communication power level from the power source.
 41. Themethod of claim 39, wherein processing the received time spaced analyterelated signals comprises determining a rate of change of the monitoredanalyte level.
 42. The method of claim 41, wherein processing thereceived time spaced analyte related signals further comprises comparingthe rate of change of the monitored analyte level to a stored adversecondition parameter.
 43. The method of claim 39, wherein the detectedadverse condition includes one or more of an impending hypoglycemiccondition, a hypoglycemic condition, or a hyperglycemic condition. 44.The method of claim 39, wherein the wireless communication module isconfigured to transmit with a greater transmission range at the secondpower level than at the first power level.
 45. The method of claim 39,wherein the remotely located device is a reader device or a mobilephone.
 46. The method of claim 39, wherein processing the received timespaced analyte related signals is performed by an application specificintegrated circuit (ASIC).
 47. The method of claim 39, wherein themonitored analyte level is a monitored glucose level.
 48. The method ofclaim 39, wherein the wireless communication module is configured totransmit the one or more of the received time spaced analyte relatedsignals and the generated notification signal according to a Bluetoothor Bluetooth Low Energy protocol.